This project focuses on basic and applied research on HIV-1. It covers two broad areas: I) basic research studying the regulated expression of HIV-1; and II) applied research towards developing small molecular inhibitors targeted against HIV-1. Some notable scientific advances from our research program in 2007-2008 include: 1) studies on understanding the role of RNA interference in HIV-1 replication; 2) examination of the role of RNA-cap methylation on HIV-1 replication; and 3) the development of targeted inhibitors of HIV-1 replication with the discovery of several anti-RNA helicase compounds.